This project is concerned with the investigation of the relationship between cytomegalovirus and human malignancy and the study of the mechanisms of human cytomegalovirus oncogenesis. The approach is based on our recent development work and can be categorized as follows: a) Detection of the existence of human CMV genome in cervical cancer, prostate tumor, salivary gland tumor, colon carcinoma, Kaposi's Sarcoma and Hodgkin's disease-involved organs by nucleic acid hybridization techniques; b) Observation of virus and cell interaction by transforming human fibroblasts with CMV isolation from various tumor tissues (strains: Mj, Kap-9, and UNC #509). The alteration of cell-surface protein in virus infected and transformed cells will be examined by tissue culture total labeling and by the lactoperoxidase catalyzed iodination of the cell membrane and SDS-polyacrylamide gel electrophoresis analysis. Virus genome status will be also examined. c) Detection and characterization of virus genome and message in CMV transformed fibroblasts by DNA-DNA reassociation kinetics analysis; d) Comparison and analysis of oncogenic human CMV strain with prototype CMV by nucleic acid hybridization, restriction endonuclease cleavage analysis and immunological approach; e) Designation of the viral DNA restriction fragment which is responsible for the virus oncogenesis. Transformation of human fibroblasts with restriction endonuclease generated DNA fragments by calcium phosphate precipitation technique will be use to approach this subject. These approaches should provide the necessary first step for an understanding of the phenomenon of the oncogenesis of human cytomegalovirus, increasingly recognized as an important human pathogen.